维甲酸和甘草酸联合对人肺癌细胞增殖和侵袭抑制作用的研究

Proliferation Inhibition and Anti-invasion Effect of Retinoic Acid and Glycyrrhizin in Human Lung Cancer Cell Line

目的 探讨全反式维甲酸和甘草酸单独及联合作用对高转移人肺癌细胞 (PGCL3 )增殖和侵袭的抑制作用。方法 用维甲酸和甘草酸处理PGCL3细胞 ,通过细胞增殖抑制试验、软琼脂集落形成试验、侵袭、运动和黏附试验、以及组织蛋白酶B活性的测定 ,观察PGCL3细胞增殖和侵袭能力的变化。结果 维甲酸和甘草酸可减弱PGCL3细胞增殖能力 ,并呈剂量依赖性 ,半抑制浓度IC50 分别为 12 .6μmol/L和 1.8mmol/L。 2 .5 μmol/L和 5 .0 μmol/L维甲酸、0 .5mmol/L和 1.0mmol/L甘草酸能抑制PGCL3细胞的侵袭能力 (P <0 .0 5和P <0 .0 1) ,且有剂量依赖性。 5 .0 μmol/L维甲酸和 0 .5mmol/L甘草酸联合作用对PGCL3细胞的侵袭抑制率高于两药单独作用之和 ,呈协同作用。上述浓度甘草酸对细胞的运动、黏附、组织蛋白酶B分泌和软琼脂集落形成率均有显著抑制作用 (P <0 .0 1)。结论 维甲酸和甘草酸对PGCL3细胞的增殖和侵袭有抑制作用 ,两药有协同作用 ,甘草酸抗侵袭机理不是对侵袭的某一环节的阻断 。

Objective To study the effects on proliferation inhibition and anti invasion of retinoic acid(RA) and glycyrrhizin(GL) single or combined,in highly metastasis lung cancer cell line(PGCL3).Methods The proliferation inhibitive rate,the colony formation rate in soft agar,the invasive ability to reconstituted basement membrane,the chemotatic migration ability,the laminin adhesion ability,and the activity of cathepsin B(CB) were tested.Results Treated with RA and GL,the proliferation of PGCL3 cells was inhibited obviously,and the inhibition degree was related to dose of the drugs.IC50 of the proliferation inhibition was 12.6 μmol/L and 1.8 mmol/L respectively.Treated with 2.5 μmol/L,5.0 μmol/L RA and 0.5 mmol/L,1.0 mmol/L GL,the invasive ability was decreased significantly( P <0.05 and P <0.01),and the inhibition was in a dose dependent manner.In combined treatment with 5.0 μmol/L RA and 0.5 mmol/L GL,the inhibition of invasion was greater than the sum of single treatment with the two drugs.Treated with GL of above concentration,the adhesion and migration ability,the secretion of CB and the colony formation rate in semi solid agar of the PGCL3 cells were decreased significantly( P <0.01).Conclusion RA and GL can inhibit the proliferation and invasion of the PGCL3 human lung cancer cells,and their effects of anti invasion is of synergism.The mechanism of anti invasion of GL is to inhibit many points of invasive process.